Inflammation is tightly regulated by a vast system that is intricately interconnected with innate immunity. Aberrations in expression or signaling, such as in innate immune receptors, can create excessive inflammation and, when chronic, often promote oncogenesis. The triggering receptor expressed on myeloid cells receptor family has been characterized as a major player in the amplification and signaling of the inflammatory response. In a number of chronic inflammatory conditions and malignancies, the triggering receptor expressed on myeloid cells has been implicated in disease severity and progression. In this article, the current understanding of triggering receptor expressed on myeloid cells function in pre-malignant, malignant and chronic inflammatory conditions is critically reviewed. The potential for therapeutic application is also discussed.